Normal mitochondrial respiration generates as a byproduct reactive oxygen species (ROS) such as O2-, H2O2 and the particularly reactive OH free radical. According to the oxidative damage theory, ROS-induced damage to biomolecules is a major cause of aging1,2. The cellular free iron pool can contribute to ROS by catalyzing the Fenton reaction, where Fe(II) is oxidized by H2O2 to Fe(III), generating the OH free radical. Taken together, this suggests that iron homeostasis might protect against aging. Ferritins regulate the cytosolic concentration of iron by sequestering excess iron, and can provide protection against oxidative stress in some contexts3,4. C. elegans has two ferritin genes,
ftn-1 and
ftn-2 (ref. 5). Long-lived
daf-2 mutants show a ~50-fold increase in
ftn-1 mRNA levels, raising the possibility that
ftn-1 might contribute longevity assurance. We have therefore tested the role of
ftn-1 in longevity assurance. We find that RNAi of
ftn-1, alone or with
ftn-2, does not reduce
daf-2 mutant longevity, nor does over-expression of
ftn-1 increase lifespan. We have used electron paramagnetic resonance spectroscopy (EPR) to verify that
ftn-1 over-expression lowers free iron levels in vivo. This also results in resistance to peroxide [(CH3)3COOH] toxicity, consistent with reduced Fenton chemistry. Similar results were obtained using iron chelator treatment protocols. Overall, these results show that ferritin does not contribute to longevity assurance, and imply that free iron levels and oxidative damage induced via the Fenton reaction are not critical determinants of aging in C. elegans. This is consistent with other, recent studies casting doubt on the importance of ROS in aging in C. elegans (reviewed in ref. 6). 1. J Gerontol 11, 298 (1956). 2. Physiol Rev 78, 547 (1998). 3. J Biol Chem 275, 25122 (2000). 4. J Biol Chem 267, 18148 (1992). 5. J Biol Chem 278, 3227 (2003). 6. Cell Cycle 8, 1681 (2009).